Proanthocyanidins and Related Compounds: Antileishmanial Activity and Modulatory Effects on Nitric Oxide and Tumor Necrosis Factor-.ALPHA.-Release in the Murine Macrophage-Like Cell Line RAW 264.7.

Abstract

A series of 17 proanthocyanidins and structurally related compounds was tested for activity against Leishmania donovani amastigotes and promastigotes in vitro. Most of the polyphenols significantly inhibited the intracellular survival of L. donovani amastigotes (EC 50 0.8-10.6 nM) when compared with the antileishmanial drug Pentostam ® (EC 50 10.6 nM), but all were inactive against the extracellular form (EC 50 7.8 to Ͼ86 nM). Noteworthy is that all compounds exhibited only moderate or no cytotoxicity against the murine host cells (EC 50 7.8 to Ͼ56 nM; Ͼ25 m mg/ml). These polyphenols were further evaluated for immunomodulatory effects on macrophage functions, including release of nitric oxide (NO), tumor necrosis factor-a a (TNF) and interferon (IFN)-like properties using several functional assays. The results showed that all compounds induced murine RAW 264.7 cells only moderately to release NO (7-26 m mM) relative to the reference stimulus IFN-g g/LPS (119 m mM). The TNF-inducing potential of the polyphenols producing 50% lysis in murine L929 cells ranged from absent to 138 U/ml at the host cell subtoxic concentration of 50 m mg/ml. The highest TNF-inducing activity was associated with those flavan-3-ols with galloyl groups (98-127 U/ml). For proanthocyanidins, it appeared that an increase in the flavanyl chain length did not enhance the induction of TNF-release (32-86 U/ml and below detection limits for oligomers and polymers, respectively). With interferon-like activities, phylloflavan and a prodelphinidin polymer showed appreciable cytoprotective effects, as reflected by the inhibition of the cytopathic effect of encephalomyocarditis virus on L929 fibroblast cells (38 and 36 U/ml, respectively). All remaining compounds displayed only negligible or moderate protective effects at subtoxic concentrations up to 25 m mg/ml (Ͻ5 to 12 U/ml). These results indicate that proanthocyanidins and related compounds have favorable antileishmanial activity in vitro and might be considered as beneficial immunological response modifiers provided there are no bioavailability problems.

Anti-inflammatory and Anti-melanogenic Proanthocyanidin Oligomers from Peanut Skin

“…17) Proanthocyanidin oligomers have a variety of biological effects, including anti-allergic 8,18) and anti-oxidative activity. 19) Kolodziej et al, 20) have reported that 17 proanthocyanidins (types B and C) strongly suppressed the production of nitric oxide, TNF, and interferon (IFN)-γ in a cultured murine macrophage cell line (RAW 264.7) co-stimulated with INF-γ and LPS. In our study, some type A proanthocyanidins, especially compound 4 from peanut skin, strongly suppressed the production of inflammatory cytokines, whose activities were stronger than that of proanthocyanidin B-3 (9).…”

Triterpenoidal alkaloids from Buxus hyrcana and their enzyme inhibitory, anti-fungal and anti-leishmanial activities

“…Anti-fungal assays were carried out using a progressive double dilution method (Ata et al, 2009a). All of the isolated compounds were also screened for their leishmanicidal activity using previously reported methods with a slight modification (Kolodziej et al, 2001).…”

In vitro antileishmanial and antitrypanosomal activities of five medicinal plants from Burkina Faso

“…Several studies have shown that alkaloids (González-Coloma et al 2011;Kam et al 1999;Mohammad et al 2003), flavanones (Grecco et al 2010), chalcones (Kayser and Kiderlen 2001;Liu et al 2003), di-and triterpenoids (Tan et al 2002), saponins (Ridoux et al 2001), and polyphenols (Kolodziej et al 2001) are phytochemical compounds with antileishmanial effect. Our previous study showed that L. ukambensis contained a high concentration of polyphenols, triterpenes, and saponins (Sawadogo et al 2011).…”